Comparison of testing approaches for Clostridium difficile infection at a large community hospital.

Multiple diagnostic approaches are available for Clostridium difficile infection (CDI); current guidelines support two-step testing (2ST) as the preferred approach. We retrospectively evaluated the impact of switching from toxin enzyme immunoassay (EIA) to 2ST, and then to polymerase chain reaction (PCR), on CDI rates, test utilization and CDI treatment at a 900-bed tertiary care community teaching hospital. All inpatients tested for CDI between December 2008 and February 2011 were included. A positive toxin EIA or PCR was diagnostic of CDI; 2ST was performed using glutamate dehydrogenase EIA, followed by PCR if positive. Repeat tests within 8 weeks on the same patient were considered part of the same testing episode. Data were collected electronically and studied in aggregate from 9725 unique inpatients tested for CDI, representing 20 836 individual tests. PCR detected 41% more patients with CDI than toxin EIA (p <0.0001), and 15% more than 2ST (p 0.02), corresponding to higher hospital-onset and community-onset CDI rates. The number of CDI tests performed per patient decreased by 48% with PCR (p <0.0001) compared with toxin EIA. For patients with CDI, time to the first positive test result was shortest with PCR. For patients without CDI, a negative PCR, but not 2ST, was associated with 22% fewer CDI treatment days, compared with toxin EIA (p <0.0001). Compared with both toxin EIA and 2ST, PCR detected more CDI patients faster and with less frequent testing, and negative PCR results were associated with less empirical CDI treatment.

A20 inhibits NF-kappa B activation downstream of multiple Map3 kinases and interacts with the I kappa B signalosome.

A20, a TNF inducible gene, inhibits TNF-mediated apoptosis as well as NF-kappa B induced by this cytokine. Reporter assay experiments revealed that A20 is a very effective inhibitor of NF-kappa B signaling induced by TRAFs and several Map3 kinases, including NIK, MEKK1, COT, and TAK1. Similarly, the NF-kappa B inducing activity of TAX, an activator of the I kappa B kinase complex, is also abrogated by A20. Inhibition of NF-kappa B is specific as A20 has no effect on TNF-alpha-induced JNK activation. These results suggest that the molecular target of A20 is more distal to the receptor than TRAFs as previously proposed. A20 inhibits NF-kappa B-dependent transcription without a concomitant decrease in nuclear NF-kappa B DNA binding activity or nuclear translocation of p65. This apparent discrepancy between transcriptional readout and gel shift experiments is observed with a variety of stimuli, including expression of IKK beta. Therefore, in addition to the phosphorylation of I kappa B, another signal is needed for transcriptional activation of NF-kappa B. A20 inhibits this non-redundant signal. The observation that A20 associates with IKK alpha and is phosphorylated upon IKK beta co-expression may suggest that A20 interferes with some aspects of signalosome function.

Isolation of a Nodulisporium species from a case of cerebral phaeohyphomycosis.

A fungal infection of the brain of a 55-year-old male patient is reported. The lesion and involved fungus were located exclusively in the right medial temporo-parietal region. The patient was successfully treated with surgical resection of the lesion and antifungal chemotherapy. Few pathogenic dematiaceous fungi exhibit neurotropism and can cause primary infection in the central nervous system (CNS). The etiological agent is described as a Nodulisporium species. To date Nodulisporium has never been reported as an agent of CNS infection in humans.

The epidemiology of invasive pulmonary aspergillosis at a large teaching hospital.

OBJECTIVE: To characterize the epidemiology of invasive pulmonary aspergillosis (IPA). DESIGN: A retrospective case series. SETTING: An 850-bed, academic, tertiary-care medical center. PARTICIPANTS: Adult inpatients, between January 1, 1990, and December 31, 1998, with either a histopathology report consistent with IPA or a discharge diagnosis of aspergillosis. METHODS: We reviewed medical records and categorized case-patients as definitive or probable and acquisition of IPA as nosocomial, indeterminate, or community using standard definitions. To determine the rate of aspergillus respiratory colonization, we identified all inpatients who had a respiratory culture positive for Aspergillus species without a histopathology report consistent with IPA or a discharge diagnosis of aspergillosis. Three study intervals were defined: interval 1, 1990 to 1992; interval 2, 1993 to 1995; and interval 3, 1996 to 1998. Carpeting in rooms for patients following heart-lung and liver transplant was removed and ceiling tiles were replaced during interval 1; a major earthquake occurred during interval 2. RESULTS: 72 case-patients and 433 patients with respiratory colonization were identified. Acquisition was nosocomial for 18 (25.0%), indeterminate for 9 (12.5%), and community-acquired for 45 (62.5%) case-patients. Seventeen (23.6%) of the 72 case-patients had prior transplants, including 15 solid organ and 2 bone marrow. The IPA rate per 100 solid organ transplants (SOTs) decreased from 2.45 during interval 1 to 0.93 during interval 2 and to 0.52 during interval 3 (chi-square for trend, 5.44; P<.05). The hospitalwide IPA rate remained stable at 0.03 per 1,000 patient days. CONCLUSIONS: The SOT IPA rate decreased after intervals 1 and 2, although the hospitalwide IPA rate remained stable during the study period. Post-earthquake hospital demolition and construction occurring after interval 2 was not associated with an increase in the rate of IPA at our institution.

Plants used as antidotes by the tribals of bihar.

The paper deals some ethnomedicinal plants of Bihar which used as antidote in traditional phytotherapy.

Dhanwantari: the God of Hindu medicine.

The original conception of Ayurveda in its entirety is essentially linked to Dhanwantari who is considered as God of Hindu Medicine. Dhanwantari is considered a mythical deity born with ambrosia in one hand and Ayurveda on the other at the end of the churning of milk ocean. He reincarnated himself in the Chandra dynasty. He was born to King Dhanwa, learnt Ayurveda from Bharadwaja. His great grandson Divodasa was also known as Dhanwantari, but was specialised only in surgical branch of Ayurveda. Sushruta, is said to have learnt the art of science of surgery from Divodasa Dhanwantara.

In vitro candidastatic properties of the human neutrophil calprotectin complex.

Microbiostatic mechanisms may contribute substantially to host defense against infection by certain microbes. We studied the candidastatic activity of human neutrophils, neutrophil cytosol, and neutrophil-derived "calprotectin," a cytosolic protein complex comprised of two subunits, MRP8 and MRP14. Intact neutrophils, neutrophil lysates (prepared by ultrasonic disruption, freezing and thawing, or nonionic detergent extraction), and granule-depleted neutrophil cytosol were effective in restricting the growth of Candida albicans in a nutrient-rich tissue culture medium, RPMI 1640. Neither a subcellular fraction enriched in neutrophil granules nor selected purified granule components (lactoferrin, myeloperoxidase, cathepsin G, leukocyte elastase, lysozyme, and defensins) exerted candidastatic activity in this medium. Gel filtration liquid chromatography, anion exchange FPLC, and SDS-PAGE showed that the fungistatic factor in neutrophil cytosol was associated with the calprotectin complex. Its antifungal effects included restriction of yeast phase and mycelial growth and inhibition of glucose incorporation by yeast phase cultures. The antifungal effects of calprotectin were sustained for over 120 h and were inhibited by zinc. However, studies with 65Zn-enriched RPMI suggested that the candidastatic effects of calprotectin were not mediated by sequestration or binding of zinc. After reversed phase HPLC, calprotectin fractions containing MRP14 exhibited fungistatic activity, whereas fractions depleted of MRP14 but enriched for MRP8 lacked fungistatic activity. The results support a potentially significant role for the calprotectin complex of neutrophil cytosol in antifungal defense and suggest that MRP14 is of key importance in that activity.

Hypolipidemic activity and toxicity of 3-methoxy-N,N'-diaminophthalamide in rodents.

3-Methoxy-N,N'-diaminophthalamide was observed to be a potent hypolipidemic agent in rodents. Serum cholesterol and triglyceride levels in rats were significantly reduced as were lipid contents of the liver, small intestine, and aorta wall. VLDL and LDL cholesterol levels were significantly reduced. Unfortunately, HDL cholesterol levels were also markedly reduced. Furthermore, acute toxicity studies showed that the compound caused marked increases in serum CP kinase activity with doses of 40 and 100 mg/kg/day in mice. This is not a property of the 2,3-dihydrophthalazine-1,4-dione, the resultant product of the N,N'-diaminophthalamides. Apparently, closing the ring results in a safer compound with elevations in HDL cholesterol levels, a desirable characteristic in effective hypolipidemic agents.

In vitro antimicrobial activity of the human neutrophil cytosolic S-100 protein complex, calprotectin, against Capnocytophaga sputigena.

Calprotectin is a complex of two anionic proteins found in abundance in the cytosol of neutrophils, certain macrophages, and oral epithelial keratinocytes. Bacteria of the genus Capnocytophaga are pathogens of periodontal origin which can cause systemic infection in neutropenic subjects. Recently, it has been observed that Capnocytophaga may be internalized by neutrophils within the cytosol rather than within a membrane-delimited phagosome. The purpose of this study was to test the in vitro antibacterial effect of the cytosolic complex, calprotectin, against Capnocytophaga sputigena. Calprotectin was purified from the cytosol of human neutrophils by gel filtration and anion exchange FPLC, and it exerted potent in vitro antimicrobial effects against C. sputigena. Net bacteriostatic activity was exerted up to 18 h, after which bactericidal effects were observed. Both net bacteriostatic and bactericidal activity occurred at concentrations above 20 micrograms/mL and exhibited identical dose-response characteristics. Particle counts increased in the presence of calprotectin, despite net bacteriostasis as assessed by changes in colony-forming units (CFU). Dose-response characteristics and direct particle counts suggested that net bacteriostatic effects were the result of balanced cell division and death, rather than suspension of cell division. We conclude that calprotectin can be a significant contributor to host defense against infection by Capnocytophaga.

A systematic approach to the classification of diseases.

Ayurvedic texts have adopted multiple approaches to the classification of diseases. Caraka while choosing a binary classification in Vimana sthana declares that the classifications may be numerable and innumerable basing on the criteria chosen for such classification. He gives full liberty to the individual to go in for the newer and newer classification, provided the criteria are different. Taking cue from this statement an attempt has been made at categorizing the diseases mentioned in Ayurvedic texts under different systems in keeping with the current practice in the Western Medical Sciences.

Ayurvedic concept of hridroga its present relevance.

Hridroga is among those diseases mentioned in Ayurveda where in the description is quite brief and the Ayurvedic view point needs clarification. In view of the increasing evidence of cardiac disorders in the present times this aspect assumes added importance. Among the five types of Hridroga described, in Vatika variety Ayurveda seems to have conceived the disease entity that comes under Ischemic Heart Disease. None of the other Cardiac afflictions seem to have been described under Hridroga. It seems that a few of the presenting features based on this Acute/important/predominant nature have been described Vatika Sotha and Swasa. It looks as though pain dominating heart disease is conceived as Hridroga. When oedema is found to be the main presenting feature it is kept under Vatika sotha and when Dysponea is the main symptom it is described as Swasa. The present article undertakes to discuss this point in detail, based on Ayurvedic concepts as well as current knowledge on medicine.

Treatment of severe falciparum malaria during pregnancy with quinidine and exchange transfusion.

Malaria during pregnancy may be associated with significant morbidity and mortality in both mother and fetus. Treatment of severe chloroquine-resistant malaria during pregnancy may be problematic since quinine and related compounds may have a deleterious effect on the course of labor. This article reports the case of a 21-year-old primigravida Liberian woman who presented with high-grade (greater than 12%) parasitemia with Plasmodium falciparum. The patient was initially treated with chloroquine; however, she developed bilateral pulmonary infiltrates and premature labor, and her condition appeared to clinically deteriorate. Therapy was changed to intravenous quinidine, and red blood cell exchange transfusion was instituted. This resulted in a decreased parasitemia and clinical improvement. The patient underwent a cesarean section, and a healthy child was delivered. Although most cases of malaria may be managed with conventional chemotherapy, the use of intravenous quinidine in combination with exchange transfusion with careful monitoring should be considered in selected cases of severe, complicated malaria in pregnant women.

Relationship between acute myelomonoblastic leukemia and infection due to human immunodeficiency virus.

Infection due to the human immunodeficiency virus (HIV) has been complicated by the development of acute nonlymphocytic leukemia in five patients whose cases have previously been reported; other manifestations, including preleukemia, myelofibrosis, and myeloid hyperplasia, have also been reported in patients infected with HIV. We report the sixth case of an HIV-infected patient who developed acute myelomonocytic leukemia; HIV infection was documented by tests for serum antibodies (enzyme-linked immunosorbent assay and western blotting), by a markedly elevated p24 antigen level in plasma, and by cultures of CSF and peripheral blood that were positive for HIV. Furthermore, myelomonoblasts that were cultured without the addition of growth factors displayed evidence of HIV replication through the presence of p24 antigen and reverse transcriptase activity, both of which lasted for 4 weeks in the supernatant fluid of the cell cultures. This case report provides the first data indicating that HIV may infect myelomonoblasts in vivo and represents the sixth reported case of an association between HIV infection and pure acute nonlymphocytic leukemia.

Complications of corticosteroid therapy in patients with the acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

We retrospectively studied the acute toxicity of corticosteroid therapy in 23 episodes of PCP occurring in the setting of AIDS and determined the incidence of HIV-related complications following these and 16 other contemporaneous episodes of AIDS-related PCP treated with antimicrobials alone. The mean duration of corticosteroid therapy was 5.4 days and the mean total dose was 660 mg of methylprednisolone. Cryptococcus neoformans and Listeria monocytogenes infection each occurred once within one month of therapy in corticosteroid-treated patients; no other noteworthy acute corticosteroid toxicity was noted. Since all patients with imminently lethal PCP received corticosteroids, we could not assess the effect of these agents on acute mortality. After six months the rates of new AIDS-related diagnoses and of post-hospitalization mortality were equivalent in the two groups. We also have critically reviewed the available literature regarding this use of corticosteroids.

The anti-inflammatory activity of 5H-dibenz[c,e]azepine-5,7(6H)dione, 6,7-dihydro-5H-dibenz[c,e]azepine, N-benzoylbenzamide and 1H-benz[d,e]isoquinoline-1,3(2H)dione derivatives in rodents.

A series of N-substituted 5H-dibenz[c,e]azepin-5,7(6H)dione, 6-substituted 6,7-dihydro-5H-dibenz[c,e]azepine, 1H-benz[d,e]isoquinoline-1,3(2H)dione and N-benzoyl derivatives was shown to have anti-inflammatory and local analgesic activity in rodents. 6-(4-Chlorophenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated greater than 50% inhibition of induced edema and the writhing reflex at 25 mg/kg, I.P. in mice. 6-Methyl-6,7-dihydro-5H-dibenz[c,e]azepine and the N-butyl and N-pentyl derivatives of the dibenz-[c,e]azepine and N-benzoylbenzamide series demonstrated potent activity in both screens. The 1H-benz[d,e]isoquinoline-1,3(2H)diones were generally less active than the other three chemical classes of agents tested. However, the 2-(methylthio)ethyl derivative of this series demonstrates good activity in both screens. These agents appeared to be as potent as the standards, indomethacin and phenylbutazone, as anti-inflammatory agents in these animal models. Selected agents, e.g. 6-(4-methylphenyl)-5H-dibenz[c,e]azepin-5,7(6H)dione demonstrated anti-arthritic and anti-gout activities in rodents. The N-methyl and N-butyl derivatives of 6,7-dihydro-5H-dibenz[c,e]azepine afforded good anti-pleurisy activity in rats at 25 mg/kg x 2. The agents which demonstrated potent anti-inflammatory action were found to inhibit acid lysosomal hydrolytic enzyme activities in mouse liver and macrophages at 10(-5) M concentrations. Trypsin, elastase and collagenase activities were also inhibited by the derivatives. Prostaglandin synthetase activity of bovine seminal vesicles and mouse macrophages was inhibited by the compounds at 10(-5) M concentrations.

Concept of prameha/madhumeha (contradictions and compromises).

Of all the misleading statements Caraka's categorical declaration that all pramehas if not treated ends up as Madhumeha stands formost. Outlining a common samprapti for all Mutratipravrittaja Rogas appears to be the basic misleading efforts. Extremely limited description at certain points only adds to the confusion. Untiring efforts of the enthusiastic scholars to prove that Madhumeha is synonymous with Diabetes Mellitus have failed to help. The present study undertakes to discuss these aspects in detail and endeavours to come out with some solutions without compromising much on the classical concepts.

Effects of 2-(2,4-dimethylphenyl)indan-1,3-dione on serum lipoprotein and lipid metabolism of rodents.

2-(2,4-Dimethylphenyl)indan-1,3-dione was shown to be a potent hypolipidemic agent in rodents, lowering significantly both serum cholesterol and triglyceride levels at 20 mg/kg/day. The agent in vivo inhibited the enzymatic activities of ATP-dependent citrate lyase, acetyl-CoA synthetase, cholesterol-7-alpha-hydroxylase, acyl-CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. Tissue lipid levels of liver and small intestine also were reduced by the agent. The rat serum lipoprotein lipid content was modulated by the drug, which should be favorable for the removable of cholesterol from peripheral tissue for conduction to the liver for clearance from the body. Low density lipoprotein (LDL) cholesterol levels were reduced after treatment, which suggests that the agent potentially reduces deposition of cholesterol in plaques. If chemotherapy for atherosclerosis is to be successful, then the high density lipoprotein (HDL) cholesterol level needs to be elevated more than 16% to 25%, the level produced by current hypolipidemic agents. 2-(2,4-Dimethylphenyl)indan-1,3-dione offers a 75% increase in HDL cholesterol levels and a 30% reduction of LDL cholesterol levels with a suppression of de novo synthesis of lipids and a reduction of tissue cholesterol deposition.